The goal of this research proposal is to quantify basal and insulin-stimulated glucose disposal during insulin clamp studies. This will be done by determining glucose utilization at basal insulin concentrations (equal 10 muU/ml) and at steady-state plasma insulin concentrations of equal 60 muU/ml. The difference between these two values provides a direct estimate of the ability of insulin to promote glucose uptake. This approach will be used to compare basal and insulin-stimulated glucose uptake in normal subjects and in patients with non-insulin dependent diabetes mellitus (NIDDM), as well as defining the effect of variations in degree of obesity and level of habitual physical activity on these two facets of glucose disposal in experimental groups. In addition, basal and insulin-stimulated glucose uptake will be quantified before and after treatment of NIDDM with either weight reduction, sulfonylurea, or exogenous insulin. Finally, isolated adipocytes will be used to quantify basal and insulin-stimulated glucose uptake in all of the above situations, and attempts will be made to correlate these estimates of in vitro glucose metabolism with the in vivo results.